Fatal hepatic sinusoidal obstruction syndrome in a child with primary CNS lymphoma during induction therapy

Abstract

Hepatic sinusoidal obstructive syndrome (HSOS) is a lifethreatening syndrome characterized by painful liver enlargement, weight gain, and jaundice, and generally occurs as a complication of hematopoietic stem cell transplantation (HSCT) [1] and chemotherapy in Wilm’s tumor [2]. HSOS after conventional chemotherapy for malignant disease other than Wilm’s tumor is unusual. Here, we report the first case to our knowledge of a 9-yearold boy with PCNSL who developed fatal HSOS during induction therapy. A 9-year-old boy presented with a 4-month history of hyperphagia. He was admitted to our department because of headache. The patient’s body weight was 40 kg (28 % obesity compared to ideal body weight). He had gained 15 kg in body weight over the previous 4 months. A physical examination revealed left-sided hemiparesis with a decreased mental status. The Eastern Cooperative Oncology Group performance status (ECOG-PS) was 3. Laboratory and coagulation tests showed the following: AST, 20 U/L; ALT, 21 U/L; LDH, 384 IU/L; total bilirubin, 0.3 mg/dl; activated partial thromboplastin time (aPTT), 33.2 s (normal 26–36 s); prothrombin time (PT), 10.8 s (normal 10–15 s), prothrombin time in international normalized ratio (PT-INR), 1.05 (normal 0.9–1.1); AT III activity level, 115 % (normal 80–120 %). Magnetic resonance imaging of the brain showed a mass with a homogeneous enhancement located in the right frontal lobe, and this lesion reached the hypothalamus (Fig. 1a). As the leftsided hemiparesis progressed rapidly, a sub-total excision of the tumor was performed. A pathological examination of the surgical specimen revealed a monotonous population of small-sized mononuclear lymphoblastic cells (Fig. 1b). Flow cytometry analysis revealed that lymphoblasts expressed TdT, cytoplasmic CD79a, CD10, and HLA-DR, leading to the diagnosis of precursor B-cell lymphoblastic lymphoma of the right cerebral hemisphere. A bone marrow examination revealed 6 % lymphoblasts. Cerebrospinal fluid (CSF) revealed 81 cells/mm leukocytes, with 82 % lymphoblasts. He showed no evidence of immunodeficiency, and a serological test for HIV was negative. Although optimal treatment of PCNSL in children has not yet been established, the effectiveness of combination chemotherapy for lymphoblastic lymphoma has been studied [3, 4]. We decided to treat the patient according to the protocol of pediatric advanced lymphoblastic lymphoma (ALBNHL03). An induction therapy regimen based on prednisone (60 mg/m daily for 5 weeks), vincristine (VCR) (1.5 mg/m on days 8, 15, 22, and 29), cyclophosphamide (1.0 g/m on day 8), daunorubicin (40 mg/m on days 8, 15, and 22), L-asparaginase (6,000 U/m on days 9, 11, 13, 16, 18, 20, 23, 25, and 27), and triple intrathecal therapy (methotrexate, cytarabine, and hydrocortisone, 12.5, 25, and 25 mg, respectively, on days 1, 15, and 29) (Fig. 2). Although he had shown rapid-onset obesity, no dose modification was made. His left-sided hemiparesis did not change; however, his mental status improved, and CSF tumor cells became negative on day 15. On day 27 of induction therapy, he developed peripheral neuropathy with pain. We stopped the induction therapy other than prednisone thereafter. However, the total bilirubin level was elevated to 2.1 mg/dl, with massive abdominal effusion and pain in the right upper quadrant on day 29. S. Yamamoto (&) K. Akiyama N. Oyama M. Hayashi Y. Fujimoto H. Ikeda K. Isoyama Division of Pediatrics, Department of Showa University Fujigaoka Hospital, 1-30 Fujigaoka Aoba-ku, Yokohama 227-8501, Japan e-mail: shohei-y@med.showa-u.ac.jp